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|Title: ||Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes|
|Authors: ||Drexler, Jan Felix|
Corman, Victor M.
Sylverken, Augustina Angelina
|Issue Date: ||1-Oct-2013|
|Publisher: ||PNAS Direct Submission|
|Citation: ||Drexler et al. Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes. doi/10.1073/pnas.1308049110|
|Abstract: ||The hepatitis B virus (HBV), family Hepadnaviridae, is one of most
relevant human pathogens. HBV origins are enigmatic, and no
zoonotic reservoirs are known. Here, we screened 3,080 specimens
from 54 bat species representing 11 bat families for hepadnaviral
DNA. Ten specimens (0.3%) from Panama and Gabon yielded
unique hepadnaviruses in coancestral relation to HBV. Full genome
sequencing allowed classification as three putative orthohepadnavirus
species based on genome lengths (3,149–3,377 nt), presence
of middle HBV surface and X-protein genes, and sequence distance
criteria. Hepatic tropism in bats was shown by quantitative PCR
and in situ hybridization. Infected livers showed histopathologic
changes compatible with hepatitis. Human hepatocytes transfected
with all three bat viruses cross-reacted with sera against
the HBV core protein, concordant with the phylogenetic relatedness
of these hepadnaviruses and HBV. One virus from Uroderma
bilobatum, the tent-making bat, cross-reacted with monoclonal
antibodies against the HBV antigenicity determining S domain.
Up to 18.4% of bat sera contained antibodies against bat hepadnaviruses.
Infectious clones were generated to study all three
viruses in detail. Hepatitis D virus particles pseudotyped with surface
proteins of U. bilobatum HBV, but neither of the other two
viruses could infect primary human and Tupaia belangeri hepatocytes.
Hepatocyte infection occurred through the human HBV receptor
sodium taurocholate cotransporting polypeptide but could
not be neutralized by sera from vaccinated humans. Antihepadnaviral
treatment using an approved reverse transcriptase inhibitor
blocked replication of all bat hepadnaviruses. Our data suggest
that bats may have been ancestral sources of primate hepadnaviruses.
The observed zoonotic potential might affect concepts
aimed at eradicating HBV.|
|Description: ||An article published by PNAS Direct Submission and also available at doi/10.1073/pnas.1308049110|
|Appears in Collections:||College of Science|
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